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Described herein are the first total syntheses of (±)-dracocephalone A (1) and (±)-dracocequinones A (4) and B (5). The synthesis was initially envisioned as proceeding through an intramolecular isobenzofuran Diels-Alder reaction, a strategy that eventually evolved into a Lewis acid-promoted spirocyclization. This highly diastereoselective transformation set the stage for trans-decalin formation and a late-stage Suárez oxidation that produced a [3.2.1] oxabicycle suited for conversion to 1. Brønsted acid-mediated aromatization, followed by a series of carefully choreographed oxidations, allowed for rearrangement to a [2.2.2] oxabicycle poised for conversion to 4 and 5.

The development of a concise total synthesis of (±)-phyllantidine (1), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen-oxygen (N-O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early-stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N-O bond cleavage, and the rapid assembly of the butenolide found in (1) via use of the Bestmann ylide.

We report studies toward a small-molecule-catalytic approach to access atropisomeric diaryl ethers that proceeds through a C(sp2)–H alkylation using nitroalkanes as the alkyl source. A quaternary ammonium salt derived from quinine, containing a sterically hindered urea at the C-9 position, was found to effect atroposelective C(sp2)–H alkylation with moderate to good enantioselectivities across several naphthoquinone-containing diaryl ethers. Products could then be isolated in >95:5 er after one round of trituration. For several substrates that were evaluated, we obtained nitroethylated products in similar yields and selectivities.